ABSTRACT Chronic exposure of the skin to sunlight causes damage to the underlying connective tissue with a loss of elasticity and firmness. Silicon (Si) was suggested to have an important function in the formation and maintenance of connective tissue. Choline-stabilized orthosilicic acid ("ch-OSA") is a bioavailable form of silicon which was found to increase the hydroxyproline concentration in the dermis of animals. The effect of ch-OSA on skin, nails and hair was investigated in a randomized, double blind, placebo-controlled study. Fifty women with photodamaged facial skin were administered orally during 20 weeks, 10 mg Si/day in the form of ch-OSA pellets (n=25) or a placebo (n=25). Noninvasive methods were used to evaluate skin microrelief (forearm), hydration (forearm) and mechanical anisotropy (forehead). Volunteers evaluated on a virtual analog scale (VAS, "none=0, severe=3") brittleness of hair and nails. The serum Si concentration was significantly higher after a 20-week supplementation in subjects with ch-OSA compared to the placebo group. Skin roughness parameters increased in the placebo group (Rt:+8%; Rm: +11%; Rz: +6%) but decreased in the ch-OSA group (Rt: -16%; Rm: -19%; Rz: -8%). The change in roughness from baseline was significantly different between ch-OSA and placebo groups for Rt and Rm. The difference in longitudinal and lateral shear propagation time increased after 20 weeks in the placebo group but decreased in the ch-OSA group suggesting improvement in isotropy of the skin. VAS scores for nail and hair brittleness were significantly lower after 20 weeks in the ch-OSA group compared to baseline scores. Oral intake of ch-OSA during the 20 weeks results in a significant positive effect on skin surface and skin mechanical properties, and on brittleness of hair and nails.

[Show abstract][Hide abstract]ABSTRACT: Convincing evidence that silicon is a bioactive beneficial trace element continues to accumulate. The evidence, which has come from human, animal, and in vitro studies performed by several laboratories, indicate that silicon in nutritional and supra nutritional amounts promotes bone and connective tissue health, may have a modulating effect on the immune or inflammatory response, and has been associated with mental health. A plausible mechanism of action for the beneficial effects of silicon is the binding of hydroxyl groups of polyols such that it influences the formation and/or utilization of glycosaminoglycans, mucopolysaccharides, and collagen in connective tissue and bone. In addition, silicon may affect the absorption, retention or action of other mineral elements (e.g., aluminum, copper, magnesium). Based on findings from both animal and human experiments, an intake of silicon of near 25 mg per day would be a reasonable suggestion for an adequate intake that would assure its nutritional benefits. Increased intakes of silicon through consuming unrefined grains, certain vegetables, and beverages and cereals made from grains should be recognized as a reasonable dietary recommendation.

[Show abstract][Hide abstract]ABSTRACT: The effects of calcium ion and broad pH ranges on free fluoride ion aqueous concentrations were measured directly and computed theoretically. Solubility calculations indicate that blood fluoride concentrations that occur in lethal poisonings would decrease calcium below prevailing levels. Acute lethal poisoning and also many of the chronic effects of fluoride involve alterations in the chemical activity of calcium by the fluoride ion. Natural calcium fluoride with low solubility and toxicity from ingestion is distinct from fully soluble toxic industrial fluorides. The toxicity of fluoride is determined by environmental conditions and the positive cations present. At a pH typical of gastric juice, fluoride is largely protonated as hydrofluoric acid HF. Industrial fluoride ingested from treated water enters saliva at levels too low to affect dental caries. Blood levels during lifelong consumption can harm heart, bone, brain, and even developing teeth enamel. The widespread policy known as water fluoridation is discussed in light of these findings.

Data provided are for informational purposes only. Although carefully collected, accuracy cannot be guaranteed. The impact factor represents a rough estimation of the journal's impact factor and does not reflect the actual current impact factor. Publisher conditions are provided by RoMEO. Differing provisions from the publisher's actual policy or licence agreement may be applicable.

Page 1

ORIGINAL PAPERA. Barel Æ Æ M. Calomme Æ Æ A. TimchenkoK. De. Paepe Æ Æ N. Demeester Æ Æ V. RogiersP. Clarys Æ Æ D. Vanden BergheEffect of oral intake of choline-stabilized orthosilicic acid on skin, nailsand hair in women with photodamaged skinReceived: 10 January 2005/ Revised: 20 April 2005/ Accepted: 23 June 2005/Published online: 5 October 2005? Springer-Verlag 2005Abstract Chronic exposure of the skin to sunlight causesdamage to the underlying connective tissue with a loss ofelasticity and firmness. Silicon (Si) was suggested to havean important function in the formation and maintenanceof connective tissue. Choline-stabilized orthosilicic acid(‘‘ch-OSA’’) is a bioavailable form of silicon which wasfound to increase the hydroxyproline concentration inthe dermis of animals. The effect of ch-OSA on skin,nails and hair was investigated in a randomized, doubleblind, placebo-controlled study. Fifty women withphotodamaged facial skin were administered orallyduring 20 weeks, 10 mg Si/day in the form of ch-OSApellets (n=25) or a placebo (n=25). Noninvasivemethods were used to evaluate skin microrelief (fore-arm), hydration (forearm) and mechanical anisotropy(forehead). Volunteers evaluated on a virtual analogscale (VAS, ‘‘none=0, severe=3’’) brittleness of hairand nails. The serum Si concentration was significantlyhigher after a 20-week supplementation in subjects withch-OSA compared to the placebo group. Skin roughnessparameters increased in the placebo group (Rt:+8%;Rm: +11%; Rz: +6%) but decreased in the ch-OSAgroup (Rt: ?16%; Rm: ?19%; Rz: ?8%). The changein roughness from baseline was significantly differentbetween ch-OSA and placebo groups for Rt and Rm.The difference in longitudinal and lateral shear propa-gation time increased after 20 weeks in the placebogroup but decreased in the ch-OSA group suggestingimprovement in isotropy of the skin. VAS scores for nailand hair brittleness were significantly lower after20 weeks in the ch-OSA group compared to baselinescores. Oral intake of ch-OSA during the 20 weeks re-sults in a significant positive effect on skin surface andskin mechanical properties, and on brittleness of hairand nails.Keywords Photodamaged skin Æ Silicon Æ Orthosilicicacid Æ Nails Æ HairIntroductionHealthy skin impedes the penetration of microorgan-isms which can cause infections and protects againstirritants. Ageing leads to several changes in the skinand its appendages (hair, nails). These changes can bebroadly categorized as either intrinsic ageing (chrono-biological) or photoageing (actinic ageing). Intrinsicageing results in subtle but important alterations ofcutaneous function that are presumed to be due totime alone, whereas photoageing is the result ofpreventablechronic exposureradiation superimposed on intrinsic ageing. Majorchanges of photoageing occur in the dermis. A markeddecrease in collagen, glycosaminoglycans and proteo-glycans is observed combined with a degeneration ofelastic fibers (elastosis) resulting in a rough leatheryskin surface with fine and coarse wrinkles. Further-more, a loss of elasticity and an increase in mechanicalanisotropy of the skin is observed. Premature age-ing of the skin due to excessive exposure to UV lighteither from the sun or/and from sun benches is anincreasing problem [32].Silicon (Si) is a ubiquitous element present in varioustissues in the human body [1] and is present in 1–10 partsper million in hair [29] and nails [1]. Studies of silicondeprivation in growing animals indicated growth retar-dation and marked defects of bone and connective tissuetoultraviolet(UV)A. Barel Æ A. Timchenko Æ P. ClarysFaculty of Physical Education and Physiotherapy,Vrije Universiteit Brussel, Brussels, BelgiumM. Calomme (&) Æ N. Demeester Æ D. Vanden BergheDepartment of Pharmaceutical SciencesFaculty of Pharmaceutical, Biomedical and Veterinary Sciences,University of Antwerp, Universiteitsplein 1,B-2610 Wilrijk-Antwerp, BelgiumE-mail: microfar@ua.ac.beTel.: +32-3-820-2550Fax: +32-3-820-2544K. De. Paepe Æ V. RogiersFaculty of Medicine and Pharmacy,Vrije Universiteit Brussel, Brussels, BelgiumArch Dermatol Res (2005) 297: 147–153DOI 10.1007/s00403-005-0584-6

Page 2

[9]. Nutritional Si deficiency was found to decrease boththe collagen synthesis and the formation of glycosami-noglycans in bone and cartilage [7]. In vitro, the activityof prolyl hydroxylase was reported to be dependent onthe Si concentration in the medium of bone cultures,suggesting a Si-dependent pathway for collagen type Isynthesis [8]. Others have suggested a structural role ofSi in the cross-linking of glycosaminoglycans in con-nective tissue [25].Recent animal studies confirm the involvement of Siin bone metabolism both in young animals [26, 27] andin models for postmenopausal osteoporosis [15, 24].Subcutaneously implanted sponges of Si-deprived ratswere found to contain less hydroxyproline compared torats on a normal diet indicating that Si deprivation de-creases collagen formation which is associated withwound healing [28]. In addition, the activity of liverornithine aminotransferase, an important enzyme in thepathway of collagen formation, was lower in Si-deprivedrats compared to Si-adequate rats [28].Soluble Si is present as orthosilicic acid (OSA) inbeverages and water. It is stable in dilute concentrations(<10?4M) but polymerizes at higher concentrationsaround neutral pH into a range of silica species.Absorption studies indicated that only OSA is bio-available, whereas its polymers are not absorbed [16].Dietary silicates undergo hydrolysis, forming OSAwhich is readily absorbed in the gastrointestinal tract.Physiological concentrations of OSA stimulate skin fi-broblasts to secrete collagen type I [23].A stabilized form of OSA, choline-stabilized OSA(‘‘ch-OSA’’), was found to have a high bioavailability inhumans compared to other Si supplements that containpolymerized forms of OSA [3, 33]. Supplementation ofanimals with low doses of ch-OSA resulted in a highercollagen concentration in the skin [5] and in an increasedfemoral bone density [4, 6].Choline, the stabilizing agent in ch-OSA, is classifiedby the Food and Nutrition Board as an essential nutri-ent [12]. Although humans can synthesize it in smallamounts, dietary sources are needed to maintain normalhealth [2]. Choline is important for the structuralintegrity of cellular membranes since it is the precursorof phospholipids (phosphatidylcholine and sphingomy-elin) which are essential components of biologicalmembranes. One of its metabolites, betaine, participatesin the methylation of homocysteine to form methionine.Betaine is also known as an essential intracellular osm-olyte [35]. Choline directly affects nerve signaling (as aprecursor of the neurotransmitter acetylcholine), cellsignaling (as a precursor for intracellular messengerssuch as diacylglycerol or ceramide, platelet-activatingfactor and sphingosylphosphorylcholine)transport/metabolism (required in the biosynthesis ofvery low-density lipoproteins).In the present study we investigated the effect of oralintake of ch-OSA on skin, hair and nails in a random-ized, placebo-controlled double-blind study in subjectswith photo-aged facial skin.and lipidSubjects and methodsSubjectsFifty healthy Caucasian females, aged between 40 and65 years, with clear clinical signs of photo-ageing offacial skin were included in this study after written in-formed consent. The subjects were assigned to twogroups which were matched on the basis of photo type,age and actinic ageing. Subjects were randomly supple-mented with ch-OSA or a placebo in each group. Wo-men, using silicon supplements less than 3 monthsbefore the start of the trial or any food supplement otherthan the study medication during the trial, were ex-cluded. In addition, subjects following any dermato-logical or cosmetical antiageing or antiwrinkle therapyincluding collagen, hyaluronic or botox injections,chemical and laser peelings, retinoic and alpha hydroxyacid treatment during the trial, were excluded. Fur-thermore, exposure to sun benches or sunlight wasprohibited during the trial. The subjects provided a de-tailed list of all cosmetic products that they use daily.Subjects agreed not to change this daily regimen duringthe trial. On the day that noninvasive tests took place,subjects were instructed to refrain from using lotions,creams or other products on face and forearms. The trialwas started in the autumn of 2003 and was completed inthe spring of 2004.Ethical approval was obtained from the regionalEthics Committee (Academic Hospital, Vrije Universi-teit Brussel, Brussels, Belgium, protocol number 03/4entitled antiageing effect of ch-OSA on photodamagedskin in healthy volunteers). The study was carried out inaccordance to the Declaration of Helsinki (1964) chan-ged by the 29th World Medical Assembly at Tokyo(1975).TreatmentAll patients were supplemented during 20 weeks withtwo capsules daily containing either the excipiens (mi-crocrystalline cellulose pellets, Pharmatrans Sanaq AG,Switzerland) or 10 mg of silicon in the form of ch-OSApellets (Bio Minerals n.v., Belgium). Subjects were in-structed to take one capsule in the morning and anotherin the evening with a glass of water or juice. Placebo andch-OSA capsules were identical in color, taste, odor andpackaging and their content was blinded to the subjectsand investigator.SerologyBlood samples were collected from fasting subjects atbaseline and after a 20-week supplementation, using Si-free polypropylene syringes (Sarstedt, Germany) andneedles (Microlance, Becton Dickinson, Spain). Imme-diately after the sample was taken, the blood was148

Page 3

transferred into Si-free polypropylene tubes withoutanticoagulant (Sarstedt, Germany).Si concentration in serum was analyzed in one batchby electrothermal atomic absorption spectrometry withinverse longitudinal Zeeman background correction(AAnalyst 800, Perkin Elmer, Bodenseewerk, Germany).Pyrolytic-coated graphite tubes were used. The hollowcathode lamp settings were respectively 30 mA lampcurrent, 251.6 nm spectral line and 0.2 nm band width.The injected sample volume was 20 ll and signals weremeasured in the peak-area mode. Serum samples weremeasured in duplicate by standard addition. Standardsand serum dilutions were prepared in matrix modifiersolution containing 72 mg/l CaCl2(Aldrich, Belgium),1.508 g/l NH4H2PO4 (Merck, Belgium) and 0.5 g/lNa4EDTA (Aldrich, Belgium) in ultrapure water (con-ductance £ 0.08 lS). The sensitivity determined as theamount of silicon yielding a 0.0044 Abs.s signal was90 pg. A pool of serum obtained from fasting healthysubjects was analyzed on several days to determine theinter-assay c.v. and was found to be 8.7% for a mean Siconcentration of 109.09 lg/l (n=16).To evaluate the safety of oral treatment with ch-OSA,serum concentrations of urea, creatinine, uric acid, totalprotein, cholesterol, HDL-cholesterol, LDL-cholesteroland direct bilirubin, glutamic-oxalacetic transaminase(GOT), glutamic-pyruvic transaminase (GPT), gamma-glutamyltransferase (gamma-GT), cholinesterase, crea-tine kinase (CK), amylase and lipase were determined.Other parameters analyzed were sodium, calcium,phosphorus and zinc. All parameters were measured inserum at baseline and after 20 weeks of supplementation.Noninvasive methodsAll measurements were performed under standardizedconditions, i.e., room temperature of 19±2?C and arelative humidity level of 45–55%. An acclimatizationtime of at least 30 min was respected before measure-ments started. Hydration and microrelief of the skinwere evaluated on the forearm, whereas visco-elasticproperties were measured on the forehead, at baselineand after 20 weeks of supplementation, respectively,with the following noninvasive methods.Hydration level of the skin surface was measuredwith the Corneometer CM 825 (Courage-Khazaka,Colgne, Germany) [10] and visco-elastic properties ofthe skin were measured with the Reviscometer MPA 5(Courage-Khazaka, Colgne, Germany). The measuringprinciple of the Reviscometer is based on resonancerunning time. The time to propagate from transmitter toreceiver is measured (shear wave propagation time) andis expressed in arbitrary units. This parameter isdepending on the direction of the collagen fibers.Therefore, two measurements are made in a differentangle,i.e., longitudinalMechanical anisotropy is an indicator of skin photo-ageing and was evaluated by the difference betweenvs lateral measurement.longitudinal and lateral shear wave propagation time[14]. Microrelief (roughness) of the skin was measuredwith the skin visiometer SV 600 (Courage-Khazaka,Colgne, Germany). Investigated roughness parameterswere Rt (depth of roughness), Rm (maximum rough-ness) and Rz (mean depth of roughness) [11].Evaluation of hair and nail brittlenessSubjects were evaluated at baseline and after 20 weeksof supplementation; the degree of brittleness of hair andnails on a 4 point scale with ‘‘0’’ no brittle hair/nails, ‘‘1’’slight, ‘‘2’’ moderate and ‘‘3’’ severe.Statistical analysisDifferences between groups were evaluated with aMann–Whitney U test and differences within groupswere analyzed with a Wilcoxon-matched pairs signedrank test. P<0.05 was considered to be significant.ResultsThe mean age (±SD) in the placebo and the ch-OSAgroup was 49.2±4.7 years and 51.8±6.0 years, respec-tively. The mean body mass index was not significantlydifferent between both groups (placebo: 24.1±4.4, ch-OSA: 26.3±5.7).Mean baseline values of total cholesterol, LDL cho-lesterol and bilirubin were higher than the upper limit ofthe normal range in both the placebo and the ch-OSAgroup. All remaining parameters were within the normalrange at baseline and after the 20-week supplementationin both groups. Twenty-four subjects in both the placeboand the ch-OSA group completed the study. In neither ofthe two treatment groups there were adverse effects re-ported that were related to the study medication.The mean serum Si concentration was comparablefor both groups at baseline but was significantly in-creased after 20 weeks of ch-OSA supplementation(P<0.0001 vs T0 and P=0.0005 vs 20 weeks placebo,Table 1), whereas no differences were observed in theplacebo group.Skin hydration decreased significantly after supple-mentation in both groups but no differences were foundbetween the placebo and the ch-OSA group (Fig. 1).Skin roughness parameters increased in the placebogroup (Rt: +8%; Rm: +11%; Rz: +6%) but decreasedin the ch-OSA group (Rt: ?16%; Rm: ?19%; Rz:?8%). The change in roughness from baseline was sig-nificantly different between ch-OSA and placebo groupsfor Rt (?0.12 vs +0.02 mm, P<0.05) and Rm (?0.13 vs+0.05 mm, P<0.05, Fig. 2).The difference in longitudinal and lateral shearpropagation time increased after 20 weeks in the placebogroup but decreased in the ch-OSA group (P<0.05,Fig. 3).149

none of these studies were double blind nor placebo-controlled. Consequently, the obtained results couldhave been biased by seasonal influence and subjectiveevaluation.The present study is the first randomized, doubleblind and placebo-controlled study that illustrates apositive effect of an oral supplement on skin microreliefand skin anisotropy in women with photoaged skin. Thedose of ch-OSA supplementation (10 mg Si/day) waslow compared to the average daily Si intake of 20–50 mgreported previously by Pennington [21]. The major die-tary sources of Si are cereal/grain-based products andvegetables but modern food processing, includingrefining, is likely to reduce the dietary Si intake as it wasshown that fibers contribute the most to the siliconcontent in plant-based foods [30]. After ch-OSA sup-plementation the serum silicon concentration increasedwith more than 90% compared to the baseline levelwhich confirms the high bioavailability demonstrated inclinical [3, 33] and animal studies [5, 4]. In a compara-tive, bioavailability study [3], the silicon absorption froma single dose of ch-OSA (20 mg Si) was compared withcolloidal silicic acid and phytolytic silica in healthyvolunteers. Total silicon absorption was evaluated as thearea under the time curve (AUC, serum Si concentra-tion) and was found to be significantly higher for ch-OSA compared to the other silicon supplements and aplacebo. In another study [33], the bioavailability of ch-OSA was compared with a silicon-rich diet and phyto-lytic silica. After a 4-day intake of ch-OSA (10 mg Si/day), both the serum Si concentration and the urinary Siexcretion increased, whereas no increase was found afterthe intake of a Si-rich diet (45 mg Si/day, 31 days) and anormal diet (14 mg Si/day, 4 days).Fig. 2 Change in skinmicrorelief parameters(Visiometer SV 600) frombaseline, measured at theforearm, after supplementationwith placebo (n=24) or ch-OSA(n=24). Rt, depth of roughness;Rm, maximum roughness; Rz,mean depth of roughness. *P<0.05 vs placebo, Mann–Whitney U test. Mean values ±SE are givenFig. 3 Change in mechanicalskin anisotropy (ReviscometerMPA 5) from baseline,measured at the forehead, aftersupplementation with placebo(n=24) or ch-OSA (n=24).Mechanical anisotropy wascalculated as the differencebetween longitudinal andlateral shear propagation time.* P<0.05 vs placebo, Mann–Whitney U test. Mean values ±SE are given151